A Role for SERCA Pumps in the Neurobiology of Neuropsychiatric and Neurodegenerative Disorders

Abstract

Calcium (Ca²⁺) is a fundamental regulator of cell fate and intracellular Ca²⁺ homeostasis is crucial for proper function of the nerve cells. Given the complexity of neurons, a constellation of mechanisms finely tunes the intracellular Ca²⁺ signaling. We are focusing on the sarco/endoplasmic reticulum (SR/ER) calcium (Ca²⁺)-ATPase (SERCA) pump, an integral ER protein. SERCA's well established role is to preserve low cytosolic Ca²⁺ levels ([Ca²⁺]_cyt), by pumping free Ca²⁺ ions into the ER lumen, utilizing ATP hydrolysis. The SERCA pumps are encoded by three distinct genes, SERCA1-3, resulting in 12 known protein isoforms, with tissue-dependent expression patterns. Despite the well-established structure and function of the SERCA pumps, their role in the central nervous system is not clear yet. Interestingly, SERCA-mediated Ca²⁺ dyshomeostasis has been associated with neuropathological conditions, such as bipolar disorder, schizophrenia, Parkinson's disease and Alzheimer's disease. We summarize here current evidence suggesting a role for SERCA in the neurobiology of neuropsychiatric and neurodegenerative disorders, thus highlighting the importance of this pump in brain physiology and pathophysiology.

Keywords: Alzheimer’s disease; Bipolar disorder; Calcium; Central nervous system; Parkinson’s disease; SERCA; Schizophrenia.